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https://www.readbyqxmd.com/read/28641100/bruton-s-tyrosine-kinase-btk-as-a-promising-target-in-solid-tumors
#1
REVIEW
J Molina-Cerrillo, T Alonso-Gordoa, P Gajate, E Grande
Bruton's tyrosine kinase (BTK) is a non-receptor intracellular kinase that belongs to the TEC-family tyrosine kinases together with bone marrow-expressed kinase (BMX), redundant-resting lymphocyte kinase (RLK), and IL-2 inducible T-Cell kinase (ITK). All these proteins play a key role in the intracellular signaling of both B and T lymphocytes. Recently, some preclinical data have demonstrated that BTK is present in certain tumor subtypes and in other relevant cells that are contributing to the tumor microenvironment such as dendritic cells, macrophages, myeloid derived suppressor cells and endothelial cells...
June 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28640942/polyfunctional-response-by-immtac-imcgp100-redirected-cd8-and-cd4-t-cells
#2
Caroline Boudousquie, Giovanna Bossi, Jacob M Hurst, Karolina A Rygiel, Bent K Jakobsen, Namir J Hassan
The success of immune system based cancer therapies depends on a broad immune response engaging a range of effector cells and mechanisms. Immune mobilising monoclonal TCRs against cancer (ImmTAC(™) molecules, fusion proteins consisting of a soluble, affinity enhanced TCR and an anti-CD3 scFv Ab) were previously shown to redirect CD8(+) and CD4(+) T cells against tumours. Here we present evidence that IMCgp100 (ImmTAC recognising a peptide derived from the melanoma-specific protein, gp100, presented by HLA-A*0201) efficiently redirects and activates effector and memory cells from both CD8(+) and CD4(+) repertoires...
June 22, 2017: Immunology
https://www.readbyqxmd.com/read/28637024/tumor-location-impacts-immune-response-in-mouse-models-of-colon-cancer
#3
Xianda Zhao, Lihua Li, Timothy K Starr, Subbaya Subramanian
Existing preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells...
June 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636555/overcoming-resistance-to-targeted-therapy-with-immunotherapy-and-combination-therapy-for-metastatic-melanoma
#4
REVIEW
Hilary R Keller, Xin Zhang, Li Li, Helmut Schaider, James W Wells
Resistance to targeted therapy is an ongoing problem for the successful treatment of Stage IV metastatic melanoma. For many patients, the use of targeted therapies, such as BRAF kinase inhibitors, were initially promising yet resistance inevitably occurred. Even after combining BRAF kinase inhibitors with MEK pathway inhibitors to offset re-activation of the MAP kinase pathway, resistance is still documented. Similarly, outcomes with immune checkpoint inhibitors as monotherapy were optimistic for some patients without relapse or progression, yet the majority of patients undergoing monotherapy have progressive disease...
June 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28636222/recent-progress-in-immunotherapy-for-urological-cancer
#5
REVIEW
Wataru Obara, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata
Cancer immunotherapy for urological tumors had made progress for several decades, but recent advances in immunotherapy, as therapeutic vaccines or immune checkpoint inhibitors, have drastically changed the present treatment strategy. Recently, nivolumab and atezolizumab have been approved by the Food and Drug Administration for treatment of urological cancers. Additional immune checkpoint inhibitors and vaccines are being tested in clinical trials. Despite advances in these therapeutic modalities, benefits are limited to a subset of patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28636142/clinical-development-of-immunotherapy-for-prostate-cancer
#6
REVIEW
Masanori Noguchi, Noriko Koga, Tsukasa Igawa, Kyogo Itoh
Prostate cancer is the most common cancer in men, and the second leading cause of cancer-related death in Western countries. Prostate cancer-related death occurs in patients with metastatic castration-resistant prostate cancer. Although several new drugs for castration-resistant prostate cancer have been approved, each of these has prolonged survival by just a few months. Consequently, new therapies are sorely needed. Recently, it has been recognized that immunotherapy is an effective treatment for prostate cancer patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28635644/pd-1-pd-l1-blockade-therapy-for-tumors-with-downregulated-mhc-class-i-expression
#7
REVIEW
Michal Šmahel
The therapy of different advanced-stage malignancies with monoclonal antibodies blocking programmed cell death protein 1 (PD-1)/PD-1 ligand 1 (PD-L1) signaling has had an impressive long-lasting effect in a portion of patients, but in most cases, this therapy was not successful, or a secondary resistance developed. To enhance its efficacy in treated patients, predictive biomarkers are searched for and various combination treatments are intensively investigated. As the downregulation of major histocompatibility complex (MHC) class I molecules is one of the most frequent mechanisms of tumor escape from the host's immunity, it should be considered in PD-1/PD-L1 checkpoint inhibition...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635639/immune-checkpoints-as-a-target-for-colorectal-cancer-treatment
#8
REVIEW
Alessandro Passardi, Matteo Canale, Martina Valgiusti, Paola Ulivi
Anti-tumor immunity is a new line of research for the treatment of patients with solid tumors. In this field, negative regulators of the immune system called immune checkpoints play a key role in limiting antitumor immunologic responses. For this reason, immune checkpoint-inhibiting agents, such as those directed against cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed death-1 receptor (PD1) and its ligand PD-L1, have been developed as antitumor drugs, producing interesting results in preclinical and clinical studies...
June 21, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28635517/a-primer-for-oncoimmunology-immunooncology
#9
Brad Bolon, Famke Aeffner
Oncoimmunology (or immunooncology) is a burgeoning specialty of precision ("personalized") medicine designed to heighten the antitumor response of the immune system against molecules expressed excessively or only by tumor cells. This focus is necessary, as cancers are polyclonal tissues comprised of antigenically heterogeneous cells, the exact composition of which is shaped by the balance between antitumor immunity and tumor-promoting inflammation. Key targets include enhancing immune system (especially T cell) reactivity, inhibiting immune checkpoints, and promoting tumor cytolysis...
January 1, 2017: Toxicologic Pathology
https://www.readbyqxmd.com/read/28634571/current-immunotherapeutic-strategies-to-enhance-oncolytic-virotherapy
#10
REVIEW
Daniel E Meyers, Amanda A Wang, Chandini M Thirukkumaran, Don G Morris
Oncolytic viruses (OV) represent a promising strategy to augment the spectrum of cancer therapeutics. For efficacy, they rely on two general mechanisms: tumor-specific infection/cell-killing, followed by subsequent activation of the host's adaptive immune response. Numerous OV genera have been utilized in clinical trials, ultimately culminating in the 2015 Food and Drug Administration approval of a genetically engineered herpes virus, Talminogene laherparepvec (T-VEC). It is generally accepted that OV as monotherapy have only modest clinical efficacy...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28634284/co-administration-of-rankl-and-ctla4-antibodies-enhances-lymphocyte-mediated-anti-tumor-immunity-in-mice
#11
Elizabeth Ahern, Heidi Harjunpaa, Deborah Barkauskas, Stacey Allen, Kazuyoshi Takeda, Hideo Yagita, David Wyld, William C Dougall, Michele W L Teng, Mark J Smyth
Purpose: Novel partners for established immune checkpoint inhibitors in the treatment of cancer are needed to address the problems of primary and acquired resistance. The efficacy of combination RANKL and CTLA4 blockade in anti-tumor immunity has been suggested by recent case reports in melanoma. Here we provide a rationale for this combination in mouse models of cancer. <br />Experimental Design: The efficacy and mechanism of a combination of RANKL and CTLA4 blockade was examined by tumor infiltrating lymphocyte analysis, tumor growth and metastasis using a variety of neutralizing antibodies and gene-targeted mice...
June 20, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28634245/targeting-nectin-4-in-bladder-cancer
#12
(no author information available yet)
Preliminary findings from a phase I clinical trial indicate that enfortumab vedotin, an investigational antibody-drug conjugate targeting nectin-4, shows considerable efficacy in metastatic urothelial carcinoma. Robust responses were seen even among patients with disease progression on platinum chemotherapy and/or immune checkpoint blockade.
June 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28634215/vaccination-with-high-affinity-epitopes-impairs-antitumor-efficacy-by-increasing-pd-1expression-on-cd8-t-cells
#13
Christopher D Zahm, Viswa Colluru, Douglas G McNeel
Antitumor vaccines encoding self-antigens generally have low immunogenicity in clinical trials. Several approaches are aimed at improving vaccine immunogenicity, including efforts to alter encoded epitopes. Immunization with epitopes altered for increased affinity for the major histocompatibility complex (MHC) or T-cell receptor (TCR) elicits greater numbers of CD8 T cells but inferior antitumor responses. Our previous results suggested that programmed death 1 (PD-1) and its ligand (PD-L1) increased on antigen-specific CD8 T cells and tumor cells, respectively, after high-affinity vaccination...
June 20, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28634022/goals-and-objectives-of-the-italian-network-for-tumor-biotherapy-nibit
#14
Vincenzo Russo, Alberto Amadori, Marco Bregni, Luana Calabrò, Mario Paolo Colombo, Massimo Di Nicola, Pier Francesco Ferrucci, Enrico Proietti, Michele Maio, Matteo Bellone
The explosion in the immuno-oncology field, exemplified by the clinical implementation of immune checkpoint inhibitor blockade and other immunotherapeutic strategies was quickly recognized by the Italian biomedical community, thanks to the networking activities of the Italian Network for Tumor Biotherapy (NIBIT), which has been active since 2004 in the diffusion of new scientific and clinical findings in the fields of tumor immunology and immunotherapy. Numerous activities of NIBIT have also helped to overcome the hurdles associated with the clinical implementation of cancer immune-biotherapeutic strategies at the national and international levels...
June 16, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28633756/immunotherapy-the-wave-of-the-future-in-bladder-cancer
#15
Daniel P Petrylak
Urothelial cell carcinoma (UC) is one of the most common cancers and one of the most deadly. Metastatic UC is particularly hard to treat, because it is typically diagnosed when patients are elderly and have medical comorbidities. Many patients with metastatic UC are unable to receive cisplatin-based chemotherapy, due to older age at diagnosis and comorbidities, and even when platinum chemotherapy can be administered, it has limited success in prolonging survival. Recently, improved understanding of molecular targets and immunologic characteristics of urothelial tumor cells has resulted in new therapeutic approaches that may help optimize first- and second-line therapy...
June 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28633409/the-effect-of-pd-l1-testing-on-the-cost-effectiveness-and-economic-impact-of-immune-checkpoint-inhibitors-for-the-second-line-treatment-of-nsclc
#16
P N Aguiar, L Perry, J Penny-Dimr, H Babiker, H Tadokoro, R A de Mello, G L Lopes
Background: Immune checkpoint inhibitors improve outcomes compared to chemotherapy in lung cancer. Tumor PD-L1 receptor expression is being studied as a predictive biomarker. The objective of this study was to assess the cost-effectiveness and economic impact of second-line treatment with nivolumab, pembrolizumab, and atezolizumab with and without the use of PD-L1 testing for patient selection. Design: We developed a decision-analytic model to determine the cost-effectiveness of PD-L1 assessment and second-line immunotherapy versus docetaxel...
June 15, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28633191/-urothelial-cancer-update-on-systemic-treatment-options
#17
Günter Niegisch
Perioperative chemotherapy is likely to improve survival in both the neoadjuvant and the adjuvant setting. Therefore, it is an integral part of the modern treatment of patients with muscle-invasive urothelial bladder cancer. All patients who are suitable for cisplatin-based chemotherapy should be involved in a corresponding concept.Cisplatin-based combinations are standard regimens in the perioperative and palliative systemic treatment of urothelial cancer. Carboplatin is only an inferior substitute for "unfit" patients in the palliative treatment situation...
June 20, 2017: Aktuelle Urologie
https://www.readbyqxmd.com/read/28630051/dna-damage-and-repair-biomarkers-of-immunotherapy-response
#18
REVIEW
Kent W Mouw, Michael S Goldberg, Panagiotis A Konstantinopoulos, Alan D D'Andrea
DNA-damaging agents are widely used in clinical oncology and exploit deficiencies in tumor DNA repair. Given the expanding role of immune checkpoint blockade as a therapeutic strategy, the interaction of tumor DNA damage with the immune system has recently come into focus, and it is now clear that the tumor DNA repair landscape has an important role in driving response to immune checkpoint blockade. Here, we summarize the mechanisms by which DNA damage and genomic instability have been found to shape the antitumor immune response and describe clinical efforts to use DNA repair biomarkers to guide use of immune-directed therapies...
June 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28629761/cytokines-for-the-induction-of-antitumor-effectors-the-paradigm-of-cytokine-induced-killer-cik-cells
#19
Elisa Cappuzzello, Roberta Sommaggio, Paola Zanovello, Antonio Rosato
Cytokine-Induced killer (CIK) cells are raising growing interest in cellular antitumor therapy, as they can be easily expanded with a straightforward and inexpensive protocol, and are safe requiring only GMP-grade cytokines to obtain very high amounts of cytotoxic cells. CIK cells do not need antigen-specific stimuli to be activated and proliferate, as they recognize and destroy tumor cells in an HLA-independent fashion through the engagement of NKG2D. In several preclinical studies and clinical trials, CIK cells showed a reduced alloreactivity compared to conventional T cells, even when challenged across HLA-barriers; only in a few patients, a mild GVHD occurred after treatment with allogeneic CIK cells...
June 3, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28629632/rationale-for-immunological-approaches-to-breast-cancer-therapy
#20
Gwennaëlle C Monnot, Pedro Romero
Despite great advances in early detection, as well as surgical resection of breast tumours, breast cancer remains the deadliest cancer for women worldwide. Moreover, its incidence is without pair, accounting for twice as many new cancer cases as the second most prevalent cancer, colorectal carcinoma. There is therefore a strong need for new therapeutic approaches to breast cancers. Immunotherapies are novel treatment modalities which aim to use immune mediators to attack cancerous cells. Recent clinical results show that these may not only mediate tumour regressions but also cures in some cases...
June 16, 2017: Breast: Official Journal of the European Society of Mastology
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